Generally, chronic obstructive pulmonary disease (COPD) is one of pulmonary disease caused by abnormal inflammatory disease in lung resulting in the obstruction of respiratory tract. COPD gives rise to dyspnoea resulting from the hindrance from exhausting air flow and shows different characteristics for example, the poor reversibility of an airways limitation or airways obstruction, the progressive development according to elapse time etc, from the common characteristics of asthma and may be classified into a pulmonary emphysema and chronic obstructive bronchitis (Barnes P. J. 20014, Mediators of chronic obstructive pulmonary disease, Pharmacol. Rev. 56:515-548).
COPD has been reported as one of risk factor for cardiovascular morbidity and mortality and the fifth leading cause of death worldwide in 2001. The prevalence of chronic obstructive pulmonary disease based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (a ratio of FEV1 to FVC of less than 0.7) was 17.2% (men, 25.8%; women, 9.6%) among Koreans older than 45 years (Dong Soon Kim, Young Sam Kim, Ki-Suck Jung, Jung Hyun Chang, Chae-Man Lim, Jae Ho Lee, Soo-Taek Uh, Jae Jeong Shim, and Woo Jin Lew, on behalf of the Korean Academy of Tuberculosis and Respiratory Diseases, Am J Respir Crit Care Med Vol 172. pp 842-847, 2005; Don D. Sin and S. F. Paul Man, Chronic Obstructive Pulmonary Disease as a Risk Factor for Cardiovascular Morbidity and Mortality, Proc Am Thorac Soc Vol 2. pp 8-11, 2005; A Sonia Buist, Mary Ann McBurnie, William M Vollmer, Suzanne Gillespie, Peter Burney, David M Mannino, Ana M B Menezes, Sean D Sullivan, Todd A Lee, Kevin B Weiss, Robert L Jensen, Guy B Marks, Amund Gulsvik, Ewa Nizankowska-Mogilnicka, International variation in the prevalence of COPD (The BOLD Study): a population-based prevalence study, Lancet, Vol 370; 741-750, Sep. 1, 2007).
Most patients with COPD have all three pathological mechanisms (chronic obstructive bronchitis, emphysema, and mucus plugging) as all are induced by smoking, but they may differ in the proportion of emphysema and obstructive bronchitis. In developed countries, cigarette smoking is by far the most common cause of COPD, but there are several other risk factors, including air pollution (particularly, indoor air pollution from burning fuels), poor diet, and occupational exposure. COPD is characterized by acceleration in the normal decline of lung function seen with age. The slowly progressive airflow limitation leads to disability and premature death and is quite different from the variable airway obstruction and symptoms in asthma, which rarely progresses in severity.
There have been reported that the pathophysiological action and syndrome of COPD are fundamentally different from those of asthma. Although COPD and asthma both involve inflammation in the respiratory tract, there are marked differences in the nature of the inflammatory process, with differences in inflammatory cells, mediators, response to inflammation, anatomical distribution, and response to anti-inflammatory therapy, for example, (a) in respect to inflammatory cells, mast cell, eosinophils, D4+ cell (Th2), macrophages etc mainly act on the occurrence of asthma whereas neutrophils, CD8+ (Tc) etc mainly act on the occurrence of COPD; (b) in respect to inflammatory mediators, leukotriens B, histamine, IL-4, IL-5, II-13, eotaxin, RENTES, oxidative stress etc are mainly involved in the occurrence of asthma whereas TNF-alpha, IL-8, GRO-alpha etc are mainly involved in the occurrence of COPD; (c) in respect to inflammatory syndrome, asthma shows different inflammatory syndrome by acting on the overall pulmonary tract at early age, such as AHR (airway hyperresponsiveness), epithelial shedding, fibrosis, no parenchymal involvement, muscus secretion, relatively reversible airways obstruction, cough, sneezing, dyspnea etc from that of COPD, which occurs by acting on peripheral airways at adults and shows various phenomena such as, epithelial metaplasia, parenchymal destruction, relatively irreversible airways obstruction, chronic bronchitis, emphysema etc (Barnes P J (2000b) Mechanisms in COPD: differences from asthma. Chest 117(Suppl): 10S-14S; Saetta M, Turato G, Maestrelli P, Mapp C E, and Fabbri L M (2001) Cellular and structural bases of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 163:1304-1309).
Histopathological studies on COPD show a predominant involvement of peripheral airways (bronchioles) and lung parenchyma, whereas asthma involves inflammation in all airways but without involvement of the lung parenchyma. There is obstruction of bronchioles, with fibrosis and infiltration with macrophages and T lymphocytes. There is destruction of lung parenchyma, as well as an increased number of macrophages and CD8(cytotoxic) T lymphocytes (Saetta M, Di Stefano A, Turato G, Facchini F M, Corbino L, Mapp C E, Maestrelli P, Ciaccia A, and Fabbri L M (1998) CD8T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 157:822-826). Bronchial biopsies show similar changes with an infiltration of macrophages and CD8 cells and an increased number of neutrophils in patients with severe COPD (Di Stefano A, Capelli A, Lusuardi M, Balbo P, Vecchio C, Maestrelli P, Mapp C E, Fabbri L M, Donner C F, and Saetta M (1998) Severity of airflow limitation is associated with severity of airway inflammation in smokers. Am. J. Respir. Crit. Care Med. 158:1277-1285).
In contrast to asthma, eosinophils are not prominent except during exacerbations or when patients have concomitant asthma (Fabbri L, Beghe B, Caramori G, Papi A, and Saetta M (1998) Similarities and discrepancies between exacerbations of asthma and chronic obstructive pulmonary disease. Thora×53:803-808; Fabbri L M, Romagnoli M, Corbetta L, Casoni G, Busljetic K, Turato G, Ligabue G, Ciaccia A, Saetta M, and Papi A (2003) Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 167:418-424.).
Accordingly, the therapeutic approach of Chronic obstructive pulmonary disease (COPD) shall be different from that of asthma, however, the present therapy has been focused on treating non-specifically both of diseases. Therefore, there have been no anti-inflammatory therapies specifically approved for COPD and the available anti-inflammatory therapies were originally developed for asthma. The challenges facing research in COPD are multi-faceted; the mechanisms underlying the complex and heterogeneous pathology of this disease require unravelling; the role of inflammation in disease progression needs to be confirmed. (Hele Dj, Belvisi M G, 2003. Novel therapies for the treatment of inflammatory airway disease, Expert. Opino. Invest. Drug, 12:5-18; J Craig Fox and Mary F Fitzgerald; The role of animal models in the pharmacological evaluation of emerging anti-inflammatory agents for the treatment of COPD, Current Opinion in Pharmacology 2009, 9:231-242).
Improvements to the current therapy available to treat asthma in the form of longer acting beta-agonists, safer steroids and combination therapies are ongoing and for COPD anti-cholinergics provide symptomatic relief. Steroids have been utilised to treat exacerbations, but as yet, no treatment has been shown to impact significantly on the progressive decline in lung function in COPD or the development of asthma.
Accordingly, there have been much studied to develop new drugs with potential to successfully and specifically treat COPD till now.
The present inventors have been focused to develop potent treating agent derived from natural resources with safety and efficacy such as plant, animals etc having potent inhibiting activity from the reproduction of inflammatory cells and finally, have found that the extract of Pseudolysimachion longifolium showed potent anti-inflammatory, anti-allergy and anti-asthma activity (Korean Patent No. 10-860080) and various compounds isolated therefrom such as, verproside (6-O-3,4-dihydroxybenzoyl catalpol), picroside II (6-O-4-hydroxy-3-methoxybenzoyl catalpol), verminoside (6-O-3,4-Dihydroxy cinnamoyl catalpol), 6-O-veratroyl catalpol (6-O-3,4-Dimethoxy benzoyl catalpol), minecoside (6-O-3-hydroxy-4-methoxycinnamoyl catalpol), catalpol and the like, also showed potent anti-inflammatory, anti-allergy and anti-asthma activity (Korean Patent Publication No. 10-2006-125499).
Pseudolysimachion rotundum var subintegrum, is a perennial herb distributed in Korea, China, Japan, Ostrov Sakhalin, and Russia.
Based on the previous studies on the anti-inflammatory, anti-allergy and anti-asthma activity of the extract of Pseudolysimachion longifolium disclosed in Korean Patent No. 10-860080, the present inventors have tried to develop more efficient method for preparing more potent and more abundant ingredients showing anti-inflammatory, anti-allergy and anti-asthma activity isolated from the extract of Pseudolysimachion rotundum var subintegrum. 
However, there has been not reported or disclosed about the efficient method for preparing more potent and more abundant ingredients or the compounds isolated from the extract of Pseudolysimachion rotundum var subintegrum showing potent and specific anti-COPD activity than those in the above cited literatures, the disclosures of which are incorporated herein by reference.
Accordingly, the present inventors have found the novel industrialized method for preparing purified extract containing more abundant active ingredients such as catalpol derivatives from the extract of Pseudolysimachion rotundum var subintegrum and the purified extract or the compounds isolated therefrom showed potent anti-COPD activity without beta-2-receptor agonistic response through various in vivo tests using by BALB/c male mice, for example, an inhibition test on the proliferation and activity of inflammatory immunocyte and neutrophil recruiting to lung caused by COPD occurrence; an inhibition test on the reproduction of chemokines involved in the breakdown of pneumocyte, such as MIP-2/CXCL-2, TNF-alpha, KC/CXCL-1 (Chemokines Gro-alpha) and CXCL-8 etc; the reducing effect on the release of IL-1beta, IL-6, TNF-alpha and MMP-9 expression by decreasing NF-kappaB activation in animal test using by SPF (specific pathogen-free) Sprague-Dawley rat, as well as in vitro test, for example, an inhibition test on the expression of MUC5AC (oligomeric muscus/gel-forming), inducing effect on the IL-4-expression of Th2 cell in molecular expression profiling change test etc.